HYDROGENATION OF ESTERS TO ALCOHOLS IN THE PRESENCE OF A RU-PNN COMPLEX

Abstract

Method for hydrogenating an ester with molecular hydrogen to the corresponding alcohols in the presence of a ruthenium complex (I), wherein said complex comprises a tridentate ligand L of the general formula (II)

##STR00001##

n and m are each independently 0 or 1, and the solid-dashed double lines represent a single or double bond, with the proviso that in the case of n=1 both solid-dashed double lines represent a single bond and m is 1, and in the case of n=0 one solid-dashed double line represents a single bond and the other solid-dashed double line represents a double bond, wherein in the case of a double bond on the side facing the phenyl ring m=1, in the case of a double bond on the side facing the pyridyl ring m=0, or both solid-dashed double lines represent a single bond and m is 1.

Claims

1.-10. (canceled)

11. A method for hydrogenating an ester with molecular hydrogen to give the corresponding alcohols at a temperature of 50 to 200° C. and a pressure of 0.1 to 20 MPa abs in the presence of a five-fold or six-fold coordinated ruthenium complex (I), wherein the ruthenium complex can also be bridged to form a dimer, wherein the ruthenium complex comprises a tridentate ligand L of the general formula (II) ##STR00073## where R.sup.1, R.sup.2 are each independently an aliphatic hydrocarbon radical having 1 to 8 carbon atoms, an aromatic hydrocarbon radical having 6 or 10 carbon atoms or an araliphatic hydrocarbon radical having 7 to 12 carbon atoms, where the hydrocarbon radicals specified are unsubstituted or substituted by 1 to 3 methoxy, thiomethoxy or dimethylamino groups, and the two radicals R.sup.1 and R.sup.2 may be bonded to each other to form a 5- to 10-membered ring including the phosphorus atom, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.10, R.sup.11 are each independently hydrogen, linear C.sub.1 to C.sub.4-alkyl, branched C.sub.3 to C.sub.4-alkyl, methoxy, hydroxyl, trifluoromethyl, nitrile or dialkylamino each independently having 1 to 4 carbon atoms per alkyl group, R.sup.7, R.sup.8, R.sup.9 are each independently hydrogen, linear C.sub.1 to C.sub.4-alkyl or branched C.sub.3 to C.sub.4-alkyl, n, m are each independently 0 or 1, and the solid-dashed double lines are a single or double bond, with the proviso that in the case of n=1, both solid-dashed double lines represent a single bond and m is 1, and in the case of n=0, one solid-dashed double line represents a single bond and the other solid-dashed double line represents a double bond, wherein in the case of a double bond on the side facing the phenyl ring, m=1, in the case of a double bond on the side facing the pyridyl ring m=0, or both solid-dashed double lines represent a single bond and m is 1.

12. The method according to claim 11, wherein a ligand L (II) is used in which (i) n and m are in each case 1 and the two solid-dashed double lines represent a single bond, or (ii) n is 0 and m is 1 and the solid-dashed double line facing the phenyl ring represents a double bond and the solid-dashed double line facing the pyridyl ring represents a single bond, and both radicals R.sup.1 and R.sup.2 are phenyl, p-tolyl, 3,5-dimethyl-4-methoxyphenyl, isobutyl or cyclohexyl, the radicals R.sup.3, R.sup.4 and R.sup.6 are hydrogen, the radicals R.sup.5 and R.sup.10 are hydrogen, methyl or tert-butyl, the radical R.sup.11 is hydrogen, methyl or methoxy, and the radicals R.sup.7, R.sup.8 and R.sup.9 are hydrogen or methyl.

13. The method according to claim 11, wherein the ruthenium complex (I) comprises ruthenium in the oxidation state +2 or +3 and has the general formula (IA)
[Ru(L)X.sub.aY.sub.b].sub.pZ.sub.(p.Math.c)  (IA) where X is in each case independently a neutral monodentate ligand, where two ligands X may also be bonded to form a neutral bidentate ligand, Y is in each case independently an anionic monodentate ligand having a charge of “−1”, where Y and X together may also be an anionic bidentate ligand having a charge of “−1”, Z is in each case independently a non-coordinating anion having a charge of “−1”, where two ligands Z may also be bonded to form a non-coordinating anion having a charge of “−2”, a, b and c are each independently 0, 1, 2 or 3, and p is 1 or 2, with the provisos that a+b+c equals 1, 2, 3, 4, 5 or 6, and b and c are determined such that the ruthenium complex (IA) has a total charge of “0”.

14. The method according to claim 11, wherein the ruthenium complex (I) is obtained by reacting ligand (II) with a Ru precursor complex (IV).

15. The method according to claim 11, wherein an ester of the general formula (III) is used as ester ##STR00074## in which the radicals R.sup.a and R.sup.b are each independently a carbon-containing organic, linear or branched, non-cyclic or cyclic, saturated or unsaturated, aliphatic, aromatic or araliphatic radical which is unsubstituted or interrupted or substituted by heteroatoms or functional groups and has a molar mass of 15 to 10,000 g/mol, it also being possible for the two radicals R.sup.a and R.sup.b to be bonded to each other.

16. The method according to claim 11, wherein the ruthenium complex (I) is formed in situ from a Ru precursor complex (IV) and ligand L (II).

17. The method according to claim 11, wherein the ruthenium complex (I) is formed in situ by reaction (a) of an aldehyde or ketone of the general formula (Va) ##STR00075## with an amine of the general formula (Vb) ##STR00076## and/or (b) of an amine of the general formula (VIa) ##STR00077## with an aldehyde or a ketone of the general formula (VIb) ##STR00078## to give the ligand L (II), where the radicals R.sup.1 to R.sup.11 each have the meaning defined above, and subsequent reaction of the ligand L (II) formed, without isolation or purification thereof, with a Ru precursor complex (IV).

18. The method according to claim 11, wherein a molar ratio between the ester and the ruthenium complex (I) of 1 to 100,000 is used.

19. The method according to claim 11, wherein the hydrogenation is carried out in the presence of a base.

20. The method according to claim 19, wherein alkoxides or amides are used as base.

Description

EXAMPLES

[0211] The abbreviations given in Tables 1 to 4 are used in the following examples.

Example 1

[0212] Example 1 describes the preparation of the various ligands in the form of Examples 1.1 to 1.8.

Example 1.1 (Preparation of Ligand 1=L1)

[0213] ##STR00025##

[0214] L1 was prepared as described in Rigo et al. in Organometallics 2007, Vol. 26, pages 5636-5642.

[0215] .sup.31P-NMR (203 MHz, CD.sub.2Cl.sub.2) δ−13.9.

Example 1.2 (Preparation of Ligand 3=L3)

[0216] ##STR00026##

[0217] (2-(Diphenylphosphaneyl)phenyl)methanamine (amine A, 1.00 g, 3.43 mmol) was added at room temperature to a solution of picolinaldehyde (aldehyde A, 368 mg, 3.43 mmol) in ethanol (10 mL) and the resulting mixture stirred at room temperature for 2 hours. NaBH.sub.4 (208 mg, 5.49 mmol) was added and the mixture was stirred at room temperature for a further 2 hours. Aqueous saturated NaHCO.sub.3 solution (15 mL) and CH.sub.2Cl.sub.2 (25 mL) were then added. After phase separation, the aqueous phase was extracted with CH.sub.2Cl.sub.2 (2×25 mL). The combined organic phase was dried (Na.sub.2SO.sub.4) and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (hexane/EtOAc/NEt.sub.3, 9:1 to 1:1; a mixture of 10% NEt.sub.3 in EtOAc was used) and N-(2-(diphenylphosphaneyl)benzyl)-1-(pyridin-2-yl) methanamine (L3) was obtained as a colorless oil (600 mg, 46% yield).

[0218] .sup.1H NMR (500 MHz, CD.sub.2Cl.sub.2) δ 8.48-8.46 (m, 1H), 7.57 (td, J=7.7, 1.8 Hz, 1H), 7.54-7.51 (m, 1H), 7.36-7.30 (m, 7H), 7.28-7.24 (m, 4H), 7.19-7.10 (m, 4H), 6.91 (ddd, J=7.7, 4.5, 1.4 Hz, 1H), 4.02 (d, J=1.7 Hz, 2H), 3.79 (s, 2H). .sup.31P NMR (203 MHz, CD.sub.2Cl.sub.2) δ −15.94. HRMS (ESI) C.sub.25H.sub.23N.sub.2P ([M].sup.+): Calculated: 382.1599; Found: 382.1611.

Example 1.3 (Preparation of Ligand 4=L4)

[0219] ##STR00027##

[0220] (2-(Diphenylphosphaneyl)phenyl)methanamine (amine A, 1.53 g, 5.25 mmol) was added at room temperature to a solution of 6-methylpicolinaldehyde (aldehyde B, 636 mg, 5.25 mmol) in ethanol (20.0 mL) and the resulting mixture stirred at room temperature for 2 hours. NaBH.sub.4 (318 mg, 8.41 mmol) was added and the mixture was stirred at room temperature for a further 2 hours. Aqueous saturated NaHCO.sub.3 solution (50 mL) and CH.sub.2Cl.sub.2 (50 mL) were then added. After phase separation, the aqueous phase was extracted with CH.sub.2Cl.sub.2 (2×25 mL). The combined organic phase was dried (Na.sub.2SO.sub.4) and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (hexane/EtOAc/NEt.sub.3, 9:1 to 6:4; a mixture of 10% NEt.sub.3 in EtOAc was used) and N-(2-(diphenylphosphaneyl)benzyl)-1-(6-methylpyridin-2-yl) methanamine (L4) was obtained as a colorless oil (1.23 mg, 3.10 mmol, 59% yield).

[0221] .sup.1H NMR (500 MHz, CD.sub.2Cl.sub.2) δ 7.54-7.52 (m, 1H), 7.46 (t, J=7.7 Hz, 1H), 7.36-7.30 (m, 7H), 7.27-7.24 (m, 4H), 7.18-7.15 (m, 2H), 6.98 (d, J=7.7 Hz, 1H), 6.94 (d, J=7.7 Hz, 1H), 6.92-6.89 (m, 1H), 4.01 (s, 2H), 3.74 (s, 2H), 2.47 (s, 3H). .sup.31P NMR (203 MHz, CD.sub.2Cl.sub.2) δ −16.31. HRMS (ESI) C.sub.26H.sub.2N.sub.2P ([M].sup.+): Calculated: 396.1755; Found: 396.1777.

Example 1.4 (Preparation of Ligand 5=L5)

[0222] ##STR00028##

[0223] (2-(Diphenylphosphaneyl)phenyl)methanamine (amine A, 1.5 g, 5.14 mmol) was added at room temperature to a solution of 6-methoxypicolinaldehyde (aldehyde C, 706 mg, 5.14 mmol) in ethanol (20 mL) and the resulting mixture stirred at room temperature for 2 hours. NaBH.sub.4 (311 mg, 8.22 mmol) was added and the mixture was stirred at room temperature for a further 2 hours. Aqueous saturated NaHCO.sub.3 solution (50 mL) and CH.sub.2Cl.sub.2 (50 mL) were then added. After phase separation, the aqueous phase was extracted with CH.sub.2Cl.sub.2 (2×25 mL). The combined organic phase was dried (Na.sub.2SO.sub.4) and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (hexane/EtOAc/NEt.sub.3, 9:1 to 6:4; a mixture of 10% NEt.sub.3 in EtOAc was used) and N-(2-(diphenylphosphaneyl)benzyl)-1-(6-methylpyridin-2-yl) methanamine (L5) was obtained as a colorless oil (1.67 mg, 4.06 mmol, 79% yield).

[0224] .sup.1H NMR (500 MHz, CD.sub.2Cl.sub.2) δ 7.56-7.51 (m, 1H), 7.46 (dd, J=8.2, 7.2 Hz, 1H), 7.39-7.28 (m, 7H), 7.27-7.22 (m, 4H), 7.17 (td, J=7.5, 1.4 Hz, 1H), 6.90 (ddd, J=7.7, 4.4, 1.4 Hz, 1H), 6.71 (m, 1H), 6.56 (m, 1H), 4.01 (d, J=1.8 Hz, 2H), 3.86 (s, 3H), 3.69 (s, 2H). .sup.31P NMR (203 MHz, CD.sub.2Cl.sub.2) δ −16.25. HRMS (ESI) C.sub.26H.sub.25N.sub.2P ([M].sup.+): Calculated: 396.1755; Found: 396.1767.

Example 1.5 (Preparation of Ligand 6=L6)

[0225] ##STR00029##

[0226] 2-Picolylamine (amine 1, 715 mg, 6.61 mmol) was added at room temperature to a solution of 2-(dicyclohexylphosphaneyl)benzaldehyde (aldehyde 2, 2.00 g, 6.61 mmol) in ethanol (50 mL) and the resulting mixture stirred at room temperature for 2 hours. NaBH4 (401 mg, 10.6 mmol) was added and the mixture was stirred at room temperature for a further 2 hours. Aqueous saturated NaHCO.sub.3 solution (100 mL) and CH.sub.2Cl.sub.2 (75 mL) were then added. After phase separation, the aqueous phase was extracted with CH.sub.2Cl.sub.2 (2×50 mL). The combined organic phase was dried (Na.sub.2SO.sub.4) and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (hexane/EtOAc/NEt.sub.3, 9:1 to 3:1; a mixture of 10% NEt.sub.3 in EtOAc was used) and N-(2-(dicyclohexylphosphaneyl)benzyl)-1-(pyridin-2-yl) methanamine (L6) was obtained as a colorless oil (1.3 g, 54% yield).

[0227] .sup.1H NMR (500 MHz, C.sub.6D.sub.6) δ 8.50-8.49 (m, 1H), 7.51-7.79 (m, 1H), 7.44-7.41 (m, 1H), 7.24-7.22 (m, 1H), 7.18-7.17 (m, 1H), 7.14-7.10 (m, 2H), 6.65-6.62 (m, 1H), 4.31 (d, J=2.1 Hz, 2H), 4.03 (s, 2H), 1.95-1.87 (m, 4H), 1.70-1.53 (m, 9H), 130.-1.00 (m, 11H). .sup.31P NMR (203 MHz, CD.sub.2Cl.sub.2) δ −16.66. HRMS (ESI) C.sub.26H.sub.23N.sub.2P ([M].sup.+): Calculated: 394.2538; Found: 394.2527.

Example 1.6 (Preparation of Ligand 7=L7)

[0228] ##STR00030##

[0229] 2-Picolylamine (amine 1, 532 mg, 4.92 mmol) was added at room temperature to a solution of 2-(bis(4-methoxy-3,5-dimethylphenyl)phosphaneyl)benzaldehyde (aldehyde 3, 2.00 g, 4.92 mmol) in ethanol (50 mL) and the resulting mixture stirred at room temperature for 2 hours. NaBH.sub.4 (300 mg, 7.88 mmol) was added and the mixture was stirred at room temperature for a further 2 h. Aqueous saturated NaHCO.sub.3 solution (50 mL) and CH.sub.2Cl.sub.2 (50 mL) were then added. After phase separation, the aqueous phase was extracted with CH.sub.2Cl.sub.2 (2×25 mL). The combined organic phase was dried (Na.sub.2SO.sub.4) and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (hexane/EtOAc/NEt.sub.3, 9:1 to 6:4; a mixture of 10% NEt.sub.3 in EtOAc was used) and N-(2-(bis(4-methoxy-3,5-dimethylphenyl)phosphaneyl)benzyl)-1-(pyridin-2-yl)methanamine (L7) was obtained as a colorless oil (1.20 g, 50% yield).

[0230] .sup.1H NMR (500 MHz, C.sub.6D.sub.6) δ 8.45-8.44 (m, 1H), 7.63-7.60 (m 1H), 7.40 (ddd, J=7.6, 4.4, 1.4 Hz, 1H), 7.27 (s, 2H), 7.25 (s, 2H), 7.18-7.17 (m, 1H), 7.09-7.05 (m, 2H), 7.00-6.98 (m, 1H), 6.63-6.60 (m, 1H), 4.26 (d, J=1.9 Hz, 2H), 3.89 (s, 2H), 3.89 (s, 2H), 3.29 (s, 6H), 2.05 (s, 12H). .sup.31P NMR (203 MHz, CD.sub.2Cl.sub.2) δ −17.13. HRMS (ESI) C.sub.26H.sub.25N.sub.2P ([M].sup.+): Calculated: 498.2436; Found: 498.2441.

[0231] General Procedures 1-5 for the Hydrogenation

[0232] Procedure 1 (Isolated Ligand)

##STR00031##

[0233] 1,4-DMT=methyl 1,4-dimethylterephthalate

[0234] 1,4-BDM=1,4-benzenedimethanol

[0235] 4-HMBM=methyl 4-hydroxymethylbenzoate

[0236] 4-HMBA=4-hydroxymethylbenzaldehyde

[0237] The selected ligand (as indicated in the respective example), the selected Ru precursor (as indicated in the respective example), methyl 1,4-dimethylterephthalate (as indicated in the respective example) and NaOMe (as indicated in the respective example) were initially charged in a 100 mL autoclave under protective gas and 40 mL of toluene were added. The autoclave was sealed, a hydrogen pressure of 6.0 MPa abs was applied, and heated to the desired reaction temperature at 700 rpm (as indicated in the respective example). After reaching the desired reaction temperature, a hydrogen pressure of 8.0 MPa abs was set. After the desired reaction time had elapsed at the desired reaction temperature, the autoclave was cooled to room temperature, the discharge obtained was concentrated, the yield was optionally determined and the discharge analyzed by GC (dissolution of a sample in dioxane). Optima FFAP column (30 m×0.25 mm/0.5 μm; 15 min at 140° C. then at 20° C./min to 250° C.; flow rate: 2.0 mL/min; hydrogen as carrier gas). Conversion determination by means of GC area %. t.sub.R(1,4-BDM)=24.9 min; t.sub.R(4-HMBM)=23.0 min, t.sub.R(4-HMBA)=22.5 min.

[0238] Procedure 2 (without Isolation of the Intermediates of the Ligand L)

##STR00032##

[0239] The selected amine (as indicated in the respective example) and the selected aldehyde (as indicated in the respective example) were initially charged in a 100 mL autoclave under protective gas and 20 mL of toluene were added. The autoclave was sealed and heated to 110° C. for 2 hours. The autoclave was then cooled to room temperature and Ru precursor 1 (as indicated in the respective example), methyl 1,4-dimethylterephthalate (as indicated in the respective example) and NaOMe (as indicated in the respective example) were added. 20 mL of toluene were again added, a hydrogen pressure of 6.0 MPa abs was applied and the mixture was heated to 130° C. at 700 rpm. After the internal temperature had reached 130° C., a hydrogen pressure of 8.0 MPa abs was set. After the desired reaction time had elapsed at 130° C., the autoclave was cooled to room temperature, the discharge obtained was concentrated, the yield was optionally determined and the discharge analyzed by GC (dissolution of a sample in dioxane). Optima FFAP column (30 m×0.25 mm/0.5 μm; 15 min at 140° C. then at 20° C./min to 250° C.; flow rate: 2.0 mL/min; hydrogen as carrier gas). Conversion determination by means of GC area %. t.sub.R(1,4-BDM)=24.9 min; t.sub.R(4-HMBM)=23.0 min, t.sub.R(4-HMBA)=22.5 min.

[0240] Procedure 3 (Isolated Ligand/Substrate Screening with Base)

[0241] The selected ligand (as indicated in the respective example), the selected Ru precursor (as indicated in the respective example), the selected ester (as indicated in the respective example) and KOMe (as indicated in the respective example) were initially charged in a 100 mL autoclave under protective gas and 20 mL of toluene were added. The autoclave was sealed, a hydrogen pressure of 6.0 MPa abs was applied, and heated to the desired reaction temperature at 700 rpm (as indicated in the respective example). After reaching the desired reaction temperature, a hydrogen pressure of 8.0 MPa abs was set. After the desired reaction time had elapsed at the desired reaction temperature, the autoclave was cooled to room temperature and an aliquot of the discharge obtained was analyzed by GC. HP5 column (60 m×0.25 mm/1.0 μm; 5 min at 60° C. then at 20° C./min to 250° C.; flow rate: 2.0 mL/min; helium as carrier gas). The yield by GC was determined using tetrahydropyran (THP) as internal standard. t.sub.R(THP)=8.4 min; t.sub.R(benzyl alcohol)=13.0 min; t.sub.R(methyl benzoate)=13.6 min.

[0242] Procedure 4 (Isolated Ligand/Substrate Screening without Base)

[0243] Procedure 4 corresponds to procedure 3 with the difference that the reaction was carried out without addition of KOMe.

[0244] Procedure 5 (Isolated Ligand/Substrate Screening)

[0245] Procedure 5 corresponds to procedure 3 with the difference that the reaction was carried out in THF instead of toluene as solvent and with a different concentration ratio, and NaOMe was used as base.

[0246] The selected ligand (as indicated in the respective example), the selected Ru precursor (as indicated in the respective example), the selected ester (as indicated in the respective example) and NaOMe (as indicated in the respective example) were initially charged in a 100 mL autoclave under protective gas and 40 mL of THF were added. The autoclave was sealed, a hydrogen pressure of 6.0 MPa abs was applied, and heated to the desired reaction temperature at 700 rpm (as indicated in the respective example). After reaching the desired reaction temperature, a hydrogen pressure of 8.0 MPa abs was set. After the desired reaction time had elapsed at the desired reaction temperature, the autoclave was cooled to room temperature and an aliquot of the discharge obtained was analyzed by GC. Optima FFAP column (30 m×0.25 mm/0.5 μm; 5 min at 140° C. then at 15° C./min to 250° C.; flow rate: 2.0 mL/min; helium as carrier gas). Conversion determination by means of GC area %.

Example 2

[0247] In Example 2, the hydrogenation of methyl 1,4-dimethylterephthalate (1,4-DMT) to 1,4-benzenedimethanol (1,4-BDM) in the presence of a ruthenium complex according to procedure 1 was investigated using various previously synthesized and isolated ligands and various Ru precursors. The data of Examples 2.1 to 2.8 are shown in Table 5.

[0248] Using the ligands L1, L3 and L4 and the Ru precursors 1, 2 and 3, very high conversions of 1,4-DMT of up to >98% and very high selectivities for 1,4-BDM of up to >98% were achieved.

Example 3

[0249] In Example 3, the hydrogenation of methyl 1,4-dimethylterephthalate (1,4-DMT) to 1,4-benzenedimethanol (1,4-BDM) in the presence of a ruthenium complex according to procedure 2 (without isolating the intermediates) was investigated by preparing various ligands and using various Ru precursors. The data of Examples 3.1 to 3.5 are shown in Table 6.

[0250] Using the amines 1, 2 and 3, the aldehyde 1, from which the ligands L1, L2 and L8 are formed, and the Ru precursors 1, 3 and 4, very high conversions of 1,4-DMT of up to >98% and very high selectivities for 1,4-BDM of up to >98% were achieved.

Example 4

[0251] In Example 4, the hydrogenation of methyl benzoate to benzyl alcohol in the presence of Ru complex 1 was investigated. Ru complex 1 was used in accordance with the method described in the experimental section of P. Rigo et al., Organometallics 2007, Vol. 26, pages 5636-5642 with the title “Synthesis of trans-[RuCl.sub.2(PPh.sub.3) (b)] (1)]”.

[0252] 36.7 μmol of Ru complex 1 (30 mg), 36.7 mmol of methyl benzoate and 1.84 mmol of KOMe were initially charged in a 100 mL autoclave under protective gas and 20 mL of toluene were added. The autoclave was sealed, a hydrogen pressure of 6.0 MPa abs applied, and heated to 130° C. at 700 rpm. After reaching 130° C., a hydrogen pressure of 8.0 MPa abs was set. After 16 h at 130° C., the autoclave was cooled to room temperature and an aliquot of the discharge obtained was analyzed by GC. HP5 column (60 m×0.25 mm/1.0 μm; 5 min at 60° C. then at 20° C./min to 250° C.; flow rate: 2.0 mL/min; helium as carrier gas). The yield by GC was determined using tetrahydropyran (THP) as internal standard. t.sub.R(THP)=8.4 min; t.sub.R(benzyl alcohol)=13.0 min; t.sub.R(methyl benzoate)=13.6 min.

[0253] The following result was achieved:

[0254] Conversion of methyl benzoate: >99%

[0255] Selectivity for benzyl alcohol: 99.3%

[0256] Selectivity for benzaldehyde: 0.74%

[0257] Even when using the previously synthesized ruthenium complex, a very high conversion of >99% and a very high selectivity for benzyl alcohol of >99% were achieved in the hydrogenation of methyl benzoate to benzyl alcohol.

Example 5

[0258] In Example 5, the hydrogenation of various esters (as indicated in Table 7) in the presence of a ruthenium complex in accordance with procedures 3, 4 and 5 was investigated using various previously synthesized and isolated ligands and the Ru precursors 2, 3 and 5. Table 7 shows the data of Examples 5.1 to 5.17.

[0259] Examples 5.1 to 5.17 show that the method according to the invention may be used widely and, even when using a wide variety of esters, Ru precursors and ligands, enables high conversions and high selectivities for the corresponding alcohols.

Example 6

[0260] ##STR00033##

[0261] In Example 6, the hydrogenation of (3aR)-(+)-sclareolide to ambroxdiol was investigated.

[0262] In Examples 6.1 and 6.2, Ru complex 1 (as indicated in Table 8), (3aR)-(+)-sclareolide (as indicated in Table 8) and NaOMe (as indicated in Table 8) were initially charged in a 100 mL autoclave under protective gas and 40 mL of tetrahydrofuran were added. The autoclave was sealed, a hydrogen pressure of 6.0 MPa abs applied, and heated to the desired reaction temperature at 700 rpm (as indicated in Table 8). After reaching the desired reaction temperature, a hydrogen pressure of 8.0 MPa abs was set. After the desired reaction time had elapsed at the desired reaction temperature, the autoclave was cooled to room temperature and the solution obtained was analyzed by GC. Optima FFAP column (30 m×0.25 mm/0.5 μm; 15 min at 140° C. then at 20° C./min to 250° C.; flow rate: 2.0 mL/min; helium as carrier gas). t.sub.R(sclareolide)=29.4 min; t.sub.R(ambroxdiol)=32.5 min.

[0263] In Example 6.3, the hydrogenation of (3aR)-(+)-sclareolide to ambroxdiol in the presence of a ruthenium complex was investigated. The procedure was as in examples 6.1 and 6.2, but in contrast to examples 6.1 and 6.2, the ligand L3 and Ru precursor 3 were used instead of Ru complex 1.

[0264] Table 8 shows the data of Examples 6.1 to 6.3.

Example 7

[0265] ##STR00034##

[0266] In Example 7, the hydrogenation of isopropyl homofarnesylate to homofarnesol was investigated.

[0267] Ru precursor 5 (as indicated in Table 9) and ligand L3 (as indicated in Table 9) was initially charged in a 100 mL autoclave under protective gas and 30 mL of methanol were added. The autoclave was sealed, a hydrogen pressure of 5.0 MPa abs applied, and heated to 60° C. at 700 rpm for 1.5 hours. The pressure is then briefly released again and NaOMe and isopropyl homofarnesylate dissolved in 10 mL of methanol are added (as indicated in Table 9) under an inert atmosphere. The hydrogen pressure is then set to 5.0 MPa and the autoclave is heated to the desired reaction temperature (as indicated in Table 9) at 700 rpm. After reaching the desired reaction temperature, a hydrogen pressure of 8.0 MPa abs was set. After the specified reaction time had elapsed, the autoclave was cooled to room temperature and the solution obtained was analyzed by GC. VF-23 ms column (60 m×0.25 mm/0.25 μm; 5 min at 50° C. then at 5° C./min to 250° C.; flow rate: 1.0 mL/min; helium as carrier gas). t.sub.R(isopropyl homofarnesylate)=34.3 min; t.sub.R(homofarnesol, sum of 4 isomers)=35.1, 35.3, 35.7, 35.8 min.

[0268] Table 9 shows the data of Example 7.

Example 8

[0269] Example 8 shows the reuse of the catalyst after the removal of the product from the first hydrogenation by distillation (catalyst recycling)

[0270] 36.7 μmol of L3, 12.2 μmol of Ru precursor 5 and 36.7 mmol of methyl benzoate were initially charged in a 100 mL autoclave under protective gas and 20 mL of benzyl alcohol were added. The autoclave was sealed, a hydrogen pressure of 7.0 MPa abs applied, and heated to 130° C. at 700 rpm. After reaching the reaction temperature, a hydrogen pressure of 8.0 MPa abs was set. After a reaction time of 16 hours at 130° C. had elapsed, the autoclave was cooled to room temperature and an aliquot of the discharge obtained was analyzed by GC. HP5 column (60 m×0.25 mm/1.0 μm; 5 min at 60° C. then at 20° C./min to 250° C.; flow rate: 2.0 mL/min; helium as carrier gas). The yield by GC was determined using tetrahydropyran (THP) as internal standard. t.sub.R(THP)=8.4 min; t.sub.R(benzyl alcohol)=13.0 min; t.sub.R(methyl benzoate)=13.6 min. Conversion 99.3%; selectivity 95% benzyl alcohol.

[0271] The discharge obtained was concentrated in vacuo and then diluted again with benzyl alcohol to a total volume of 20 mL. The catalyst-containing reaction solution was transferred again to the autoclave under protective gas and another 36.7 mmol of methyl benzoate were added. A hydrogen pressure of 7.0 MPa abs was applied and the autoclave was heated to 130° C. at 700 rpm. After reaching the reaction temperature, a hydrogen pressure of 8.0 MPa abs was set. After a reaction time of 16 hours at 130° C. had elapsed, the autoclave was cooled to room temperature and an aliquot of the discharge obtained was analyzed by GC (method as described above). Conversion 97.8%; selectivity 96% benzyl alcohol.

TABLE-US-00001 TABLE 1 Ligand L Ligand [00035]   Ligand 1 = L1 [00036]   Ligand 2 = L2 [00037]   Ligand 3 = L3 [00038]   Ligand 4 = L4 [00039]   Ligand 5 = L5 [00040]   Ligand 6 = L6 [00041]   Ligand 7 = L7 [00042] [00043]   Ligand 8 = L8

TABLE-US-00002 TABLE 2 Ligand precursors Amine [00044]   Amine 1 [00045]   Amine 2 [00046]   Amine 3 [00047]   Amine A Aldehyde [00048]   Aldehyde 1 [00049]   Aldehyde 2 [00050]   Aldehyde 3 [00051] [00052]   Aldehyde A [00053]   Aldehyde B [00054]   Aldehyde C

TABLE-US-00003 TABLE 3 Ruthenium complex precursor [Ru(p- Ru(COD) cymene) (methyl- Cl.sub.2].sub.2 Ru(acac).sub.3 allyl).sub.2 p-cymene = acac = COD = 4-isopropyl- Ru(Cl).sub.2 acetyl- 1,5-cyclo- toluene (PPh.sub.3).sub.3 acetonate octadiene Ru Ru Ru Ru Ru precursor precursor 1 precursor 2 precursor 3 precursor 4 Ru.sub.3(CO).sub.12 Ru precursor 5

TABLE-US-00004 TABLE 4 Ru complex Ru complex [00055]   Ru complex 1

TABLE-US-00005 TABLE 5 (part 1): Data for examples 2.1 to 2.5 according to procedure 1 Molar ratio Molar ratio .sup.a) Reaction Ligand/Ru Substrate/Ru Conversion .sup.b) Ex. Amounts used conditions [mol/mol] [mol/mol] of 1,4-DMT Selectivity .sup.c) 2.1 0.051 mmol L1 from Example 1.1 130° C. 1.0 1000 >98% >98% for 1,4-BDM 0.026 mmol Ru precursor 1 16 h   51.5 mmol 1,4-DMT (Substrate) 2.5 mmol NaOMe 2.2 0.051 mmol L3 from Example 1.2 130° C. 1.0 1000 >98% >98% for 1,4-BDM 0.026 mmol Ru precursor 1 16 h   51.5 mmol 1,4-DMT (Substrate) 2.5 mmol NaOMe 2.3 0.051 mmol L4 from Example 1.3 130° C. 1.0 1000 >98%  97% for 1,4-BDM 0.026 mmol Ru precursor 1 16 h   51.5 mmol 1,4-DMT (Substrate) 2.5 mmol NaOMe 2.4 0.021 mmol L3 from Example 1.2 130° C. 2.0 5000 >98% >98% for 1,4-BDM 0.005 mmol Ru precursor 1 60 h   51.5 mmol 1,4-DMT (Substrate) 2.5 mmol NaOMe 2.5 0.010 mmol L3 from Example 1.2 130° C. 1.0 5000 >98% >98% for 1,4-BDM 0.005 mmol Ru precursor 1 60 h   51.5 mmol 1,4-DMT (Substrate) 2.5 mmol NaOMe .sup.a) rounded figures, .sup.b) conversion after the end of the reaction, .sup.c) selectivity after the end of the reaction

TABLE-US-00006 TABLE 5 (part 2): Data for examples 2.6 to 2.8 according to procedure 1 Molar ratio Molar ratio .sup.a) Reaction Ligand/Ru Substrate/Ru Conversion .sup.b) Ex. Amounts used conditions [mol/mol] [mol/mol] of 1,4-DMT Selectivity .sup.c) 2.6 0.051 mmol L3 from Example 1.2 130° C. 1.0 1000 >98% >98% for 1,4-BDM 0.051 mmol Ru precursor 2 16 h   51.5 mmol 1,4-DMT (substrate) 2.5 mmol NaOMe 2.7 0.051 mmol L3 from Example 1.2 130° C. 1.0 1000 >98% >98% for 1,4-BDM 0.051 mmol Ru precursors 16 h   51.5 mmol 1,4-DMT (Substrate) 2.5 mmol NaOMe 2.8 0.051 mmol L3 from Example 1.2 130° C. 1.0 1000 >98% >98% for 1,4-BDM 0.026 mmol Ru precursor 1 16 h    1% for 4-HMBA 51.5 mmol 1,4-DMT (Substrate) 2.5 mmol KOMe .sup.d) .sup.a) rounded figures, .sup.b) conversion after the end of the reaction, .sup.c) selectivity after the end of the reaction .sup.d) with KOMe instead of NaOMe

TABLE-US-00007 TABLE 6 (part 1): Data for examples 3.1 to 3.4 according to procedure 2 Molar ratio Molar ratio .sup.a) Reaction Ligand/Ru Substrate/Ru Conversion .sup.b) Ex. Amounts used conditions [mol/mol] [mol/mol] of 1,4-DMT Selectivity .sup.c) 3.1 0.064 mmol aldehyde 1 130° C. 1.28 1000 >98% >98% for 1,4-BDM 0.064 mmol amine 1 16 h   0.025 mmol Ru precursor 1 51.5 mmol 1,4-DMT (Substrate) 2.5 mmol NaOMe 3.2 0.064 mmol aldehyde 1 130° C. 1.28 1000 >98%  44% for 1,4-BDM 0.064 mmol amine 1 16 h    53% for 4-HMBM 0.05 mmol Ru precursor 3 51.5 mmol 1,4-DMT (Substrate) 2.5 mmol NaOMe 3.3 0.064 mmol aldehyde 1 130° C. 1.28 1000 >98%  97% for 1,4-BDM 0.064 mmol amine 1 16 h   0.05 mmol Ru precursor 4 51.5 mmol 1,4-DMT (Substrate) 2.5 mmol NaOMe 3.4 0.064 mmol aldehyde 1 130° C. 1.28 1000 >98% >98% for 1,4-BDM 0.064 mmol amine 2 16 h   0.025 mmol Ru precursor 1 51.5 mmol 1,4-DMT (Substrate) 2.5 mmol NaOMe .sup.a) rounded figures, .sup.b) conversion after the end of the reaction, .sup.c) selectivity after the end of the reaction

TABLE-US-00008 TABLE 6 (part 2): Data for example 3.5 according to procedure 2. Molar ratio Molar ratio .sup.a) Reaction Ligand/Ru Substrate/Ru Conversion .sup.b) Ex. Amounts used conditions [mol/mol] [mol/mol] of 1,4-DMT Selectivity.sup.c) 3.5 0.064 mmol aldehyde 1 130° C. 1.28 1000 >98% 85% for 1,4-BDM 0.064 mmol amine 3 16 h   14% for 4-HMBM 0.025 mmol Ru precursor 1 51.5 mmol 1,4-DMT (Substrate) 2.5 mmol NaOMe .sup.a) rounded figures, .sup.b) conversion after the end of the reaction, .sup.c) selectivity after the end of the reaction

TABLE-US-00009 TABLE 7 (part 1): Data for examples 5.1 to 5.4 according to procedure 3 Reaction Conversion .sup.a) Selectivity .sup.b) Ex. Amounts used Substrate conditions Alcohol of the substrate for the alcohol 5.1 Procedure 3  36.7 μmol L3 from Example 1.2  36.7 μmol Ru precursor 2  36.7 mmol of substrate  1.84 mmol KOMe [00056]   Methyl benzoate 130° C. 16 h Benzyl alcohol 99% 99% 5.2 Procedure 3 183.5 μmol L4 from Example 1.3 183.5 μmol Ru precursor 2  36.7 mmol of substrate  3.68 mmol KOMe [00057]   Methyl benzoate 130° C. 16 h Benzyl alcohol 99    97    5.3 Procedure 3 183.5 μmol L5 from Example 1.4 183.5 μmol Ru precursor 2  36.7 mmol of substrate  3.68 mmol KOMe [00058]   Methyl benzoate 130° C. 16 h Benzyl alcohol 99% 98% 5.4 Procedure 3 183.5 μmol L6 from Example 1.5 183.5 μmol Ru precursor 2  36.7 mmol of substrate  3.68 mmol KOMe [00059]   Methyl benzoate 130° C. 16 h Benzyl alcohol 99% 97% .sup.a) conversion after the end of the reaction, .sup.b) selectivity after the end oft he reaction

TABLE-US-00010 TABLE 7 (part 2): Data for examples 5.5 to 5.8 according to procedure 3 Reaction Conversion .sup.a) Selectivity .sup.b) Ex. Amounts used Substrate conditions Alcohol of the substrate for the alcohol 5.5 Procedure 3 183.5 μmol L7 from Example 1.6 183.5 μmol Ru precursor 2  36.7 mmol of substrate  3.68 mmol KOMe [00060]   Methyl benzoate 130° C. 16 h Benzyl alcohol 99% 97% 5.6 Procedure 3  36.7 μmol L3 from Example 1.2  36.7 μmol Ru precursor 2  36.7 μmol of substrate  1.84 mmol KOMe [00061]   Methyl acetate 130° C. 16 h Ethanol 99% 99% 5.7 Procedure 3  73.4 μmol L3 from Example 1.2  73.4 μmol Ru precursor 2  36.7 mmol of substrate  1.84 mmol KOMe [00062]   Methyl hexanoate 130° C. 16 h n-Hexanol 99% 97% 5.8 Procedure 3  36.7 μmol L3 from Example 1.2  36.7 μmol Ru precursor 2  36.7 mmol of substrate  1.84 mmol KOMe [00063]   Methyl nicotinate 130° C. 16 h Nicotinyl alcohol 94% 94% .sup.a) conversion after the end of the reaction, .sup.b) selectivity after the end oft he reaction

TABLE-US-00011 TABLE 7 (part 3): Data for examples 5.9 to 5.11 according to procedures 3 and 4 Reaction Conversion .sup.a) Selectivity .sup.b) Ex. Amounts used Substrate conditions Alcohol of the substrate for the alcohol 5.9  Procedure 3 183.5 μmol L3 from Example 1.2 183.5 μmol Ru precursor 2  36.7 μmol of substrate  3.68 mmol KOMe [00064]   Methyl 4-(trifluoromethyl) benzoate 130° C. 16 h 4- (Trifluoromethyl) phenyl) methanol 99% 99% 5.10 Procedure 3 183.5 μmol L3 from Example 1.2 183.5 μmol Ru precursor 2  36.7 μmol of substrate  3.68 mmol KOMe [00065]   Methyl 4-(methoxy) benzoate 130° C. 16 h (4- Methoxyphenyl) methanol 99% 99% 5.11 Procedure 4  36.7 μmol L3 from example 1.2  12.2 μmol Ru precursors  36.7 mmol of substrate [00066]   Methyl benzoate 130° C. 16 h Benzyl alcohol 99% 98% .sup.a) conversion after the end of the reaction, .sup.b) selectivity after the end oft he reaction

TABLE-US-00012 TABLE 7 (part 4): Data for examples 5.12 to 5.14 according to procedure 4 Reaction Conversion .sup.a) Selectivity .sup.b) Ex. Amounts used Substrate conditions Alcohol of the substrate for the alcohol 5.12 Procedure 4 46.6 μmol L3 from example 1.2 46.6 μmol Ru precursor 3   33 mmol of substrate [00067]   Ethyl benzoate 130° C. 16 h Benzyl alcohol 97% 99% 5.13 Procedure 4 80.4 μmol L3 from example 1.2 26.8 μmol Ru precursors 5 28.7 mmol of substrate [00068]   Dimethyl adipate 130° C. 16 h hexane-1,6-diol 99% 99% 5.14 Procedure 4  140 μmol L3 from example 1.2 46.6 μmol Ru precursors 49.9 mmol of substrate [00069]   γ-Valerolactone 130° C. 16 h 1,4-Pentanediol 97% 99% .sup.a) conversion after the end of the reaction, .sup.b) selectivity after the end oft he reaction

TABLE-US-00013 TABLE 7 (part 5): Data for examples 5.15 to 5.17 according to procedure 5 Reaction Conversion .sup.a) Selectivity .sup.b) Ex. Amounts used Substrate conditions Alcohol of the substrate for the alcohol 5.15 Procedure 5   38 μmol L3 from example 1.2   19 μmol Ru precursor 1 38.4 mmol of substrate 1.45 mmol NaOMe [00070]   Methyl levulinate 130° C. 16 h 1,4-Pentanediol >99% >99% 5.16 Procedure 5   29 μmol L3 from example 1.2   15 μmol Ru precursor 1   29 mmol of substrate 1.45 mmol NaOMe [00071]   Butyl levulinate 130° C. 16 h 1,4-Pentanediol >99%  87% 1,4-Pentanediol  13% γ-Valerolactone 5.17.sup.c) Procedure 5   35 μmol L3 from example 1.2   12 μmol Ru precursor 5 34.7 mmol of substrate 1.73 mmol NaOMe [00072]   Ethyl levulinate 130° C. 16 h 1,4-Pentanediol >99% >99% .sup.a) conversion after the end of the reaction, .sup.b) selectivity after the end of the reaction .sup.c)Ru precursor 5 and L3 were initially stirred in THF (20 mL) at 60° C. and 50 bar H.sub.2 and then the substrate was added in THF (20 mL). The rest of the procedure was then carried out as described in procedure 5.

TABLE-US-00014 TABLE 8 Data for Examples 6.1 to 6.3 Molar ratio .sup.a) Substrate/ Conversion .sup.b) Selectivity .sup.c) Amounts Reaction Ru of (Ambro- Ex. used conditions [mol/mol] sclareolide xdiol) 6.1 20 μmol 130° C. 1000 96% 90% Ru 16 h complex 1 20 mmol (3aR)-(+)- sclareolide (substrate) 1 mmol NaOMe 6.2 4 μmol Ru 135° C. 5000 97% 88% complex 1 60 h 20 mmol (3aR)-(+)- sclareolide (substrate) 1 mmol NaOMe 6.3 8 μmol L3 135° C. 5000 84% 85% from 60 h Example 1.2 8 μmol Ru precursors 40 mmol (3aR)-(+)- sclareolide (substrate) 2 mmol NaOMe .sup.a) rounded figures, .sup.b) conversion after the end of the reaction, .sup.c) selectivity after the end of the reaction

TABLE-US-00015 TABLE 9 Data for example 7 Molar ratio .sup.a) Conversion .sup.b) Selectivity .sup.c) Amounts Reaction Substrate/ of the for the Ex. used conditions Ru [mol/mol] substrate alcohol 7 200 μmol 100° C. 200 98% 94% L3 from 10 h Example 1.2 66 μmol Ru precursor 5 40 mmol isopropyl homo- famesylate 2 mmol NaOMe .sup.a) rounded figures, .sup.b) conversion after the end of the reaction, .sup.c) selectivity after the end of the reaction